The importance of Biofilms in chronic and treatment-resistant infectious disease, increasingly is clear. Biofilms also are a major problem in industrial processes. The focus of this proposal is to develop methods for discovering compounds that block and/or reverse biofilm formation, and to discover, and structurally characterize, active compounds. Specifically, we will develop efficient methods to screen extracts and compounds for their ability to regulate biofilms of a gram negative pathogen, and develop and validate new screens with biofilms of gram negative bacteria and fungi. In addition, we will evaluate plants, especially those that live in moist or wet environments, as a possible rich source of novel compounds that block or reverse biofilm formation. Compounds will be isolated and characterized with sensitive, high-throughput parallel LC-MS and LC-NMR. Once we define rich sources of compounds, effective assays, and identify new compounds that can block or reverse biofilm formation in Phase I, in Phase II we will use methods optimized here, and further characterize the biological activity of active compounds, to determine their potential for application(s) in protection against biofilm-related damage and disease, and the effectiveness of our methods for discovering valuable compounds. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE